TY - JOUR
T1 - Lot-to-lot consistency of a hexavalent DTwP-IPV-HB-PRP∼T vaccine and non-inferiority to separate DTwP-HB-PRP∼T and IPV antigen-matching vaccines at 6–8, 10–12, and 14–16 weeks of age co-administered with oral rotavirus vaccine in healthy infants in India
T2 - A multi-center, randomized, controlled study
AU - Mangarule, S.
AU - Prashanth, S.
AU - Kawade, A.
AU - Ravi, M. D.
AU - Padmavathi, I. V.
AU - Palkar, S.
AU - Tripathi, V. N.
AU - Singh, R.
AU - Maurya, M.
AU - Mitra, M.
AU - Shetty, R. S.
AU - Kompithra, R. Z.
AU - Dhaded, S. M.
AU - Epari, V.
AU - Moureau, A.
AU - Jayanth, M. V.
AU - Varghese, K.
AU - Ravinuthala, S.
AU - Kukian, D.
AU - Patnaik, B. N.
AU - Noriega, F.
N1 - Funding Information:
The authors would like to acknowledge all study staff for their contributions to the study conduct and all study participants and their parents/legal guardians. Additionally, the authors thank Julie Leclercq for assistance in the statistical analyses, Sanofi Pasteur's Global Clinical Immunology (GCI) laboratory (Swiftwater, PA, USA) for serological testing, Dr Veena G Kamath and Dr Dinesh M Nayak (co-investigators at Kasturba Medical College, Manipal), and Dr Emmanuel Vidor (Sanofi Pasteur) for his valuable input into the development of this article. The authors would also like to thank Emilia Jordanov for her contribution in the study. Dr Andrew Lane (Lane Medical Writing) provided professional medical writing assistance in the preparation and development of the manuscript in accordance with the European Medical Writers Association guidelines and Good Publication Practice and was funded by Sanofi.
Funding Information:
Financial support : The study was funded by Sanofi Healthcare India Private Ltd (SHIPL).
Publisher Copyright:
© 2022 The Authors
PY - 2022/12
Y1 - 2022/12
N2 - Background: Combination vaccines reduce the number of pediatric injections but must be as safe, immunogenic, and effective as each of the individual vaccines given separately. Additionally, consistency in manufacturing lots is essential for WHO prequalification. This study aimed to establish the lot-to-lot consistency of a fully liquid, hexavalent diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)-inactivated poliovirus (IPV)-hepatitis B (HB)-Haemophilus influenzae b (PRP-T) (DTwP-IPV-HB-PRP∼T) vaccine and to demonstrate non-inferiority to licensed DTwP-HB-PRP∼T and IPV vaccines. Methods: A Phase III, randomized, active-controlled, and open-label study was conducted at multiple centers across India. Healthy infants who had received a birth dose of oral poliovirus vaccine and hepatitis B vaccine received one of three lots of DTwP-IPV-HB-PRP∼T or separate DTwP-HB-PRP∼T and IPV vaccines at 6–8, 10–12, and 14–16 weeks of age. Oral rotavirus vaccine was co-administered at 6–8 weeks of age and 10–12/14–16 weeks of age. DTwP-IPV-HB-PRP∼T lot-to-lot consistency and non-inferiority (pooled DTwP-IPV-HB-PRP∼T) versus DTwP-HB-PRP∼T and IPV post-third dose were assessed using seroprotection rates (anti-D, anti-T, anti-HBs, anti-PRP, anti-polio 1, 2, 3) and adjusted geometric mean concentrations (anti-PT, anti-FIM). Safety was assessed by parental reports. Results: Lot-to-lot consistency was demonstrated for DTwP-IPV-HB-PRP∼T and non-inferiority versus DTwP-HB-PRP∼T and IPV was confirmed with 95% CIs for seroprotection rate differences and adjusted geometric mean concentration ratios within pre-defined clinical margins. Pooled seroprotection rate was ≥ 99.7% for anti-D ≥ 0.01 IU/mL, anti-T ≥ 0.01 IU/mL, anti-HBs ≥ 10 mIU/mL, anti-PRP ≥ 0.15 µg/mL, and anti-polio 1, 2, and 3 ≥ 8 (1/dil) and vaccine response rate was 83.9% for anti-PT and 97.7% for anti-FIM. There were no safety concerns. Conclusions: Immunogenicity of three lots of the fully liquid DTwP-IPV-HB-PRP∼T vaccine was consistent and non-inferior to licensed comparators following vaccination at 6–8, 10–12, and 14–16 weeks of age. There were no safety concerns and no evidence of any effect of co-administration with rotavirus vaccine.
AB - Background: Combination vaccines reduce the number of pediatric injections but must be as safe, immunogenic, and effective as each of the individual vaccines given separately. Additionally, consistency in manufacturing lots is essential for WHO prequalification. This study aimed to establish the lot-to-lot consistency of a fully liquid, hexavalent diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)-inactivated poliovirus (IPV)-hepatitis B (HB)-Haemophilus influenzae b (PRP-T) (DTwP-IPV-HB-PRP∼T) vaccine and to demonstrate non-inferiority to licensed DTwP-HB-PRP∼T and IPV vaccines. Methods: A Phase III, randomized, active-controlled, and open-label study was conducted at multiple centers across India. Healthy infants who had received a birth dose of oral poliovirus vaccine and hepatitis B vaccine received one of three lots of DTwP-IPV-HB-PRP∼T or separate DTwP-HB-PRP∼T and IPV vaccines at 6–8, 10–12, and 14–16 weeks of age. Oral rotavirus vaccine was co-administered at 6–8 weeks of age and 10–12/14–16 weeks of age. DTwP-IPV-HB-PRP∼T lot-to-lot consistency and non-inferiority (pooled DTwP-IPV-HB-PRP∼T) versus DTwP-HB-PRP∼T and IPV post-third dose were assessed using seroprotection rates (anti-D, anti-T, anti-HBs, anti-PRP, anti-polio 1, 2, 3) and adjusted geometric mean concentrations (anti-PT, anti-FIM). Safety was assessed by parental reports. Results: Lot-to-lot consistency was demonstrated for DTwP-IPV-HB-PRP∼T and non-inferiority versus DTwP-HB-PRP∼T and IPV was confirmed with 95% CIs for seroprotection rate differences and adjusted geometric mean concentration ratios within pre-defined clinical margins. Pooled seroprotection rate was ≥ 99.7% for anti-D ≥ 0.01 IU/mL, anti-T ≥ 0.01 IU/mL, anti-HBs ≥ 10 mIU/mL, anti-PRP ≥ 0.15 µg/mL, and anti-polio 1, 2, and 3 ≥ 8 (1/dil) and vaccine response rate was 83.9% for anti-PT and 97.7% for anti-FIM. There were no safety concerns. Conclusions: Immunogenicity of three lots of the fully liquid DTwP-IPV-HB-PRP∼T vaccine was consistent and non-inferior to licensed comparators following vaccination at 6–8, 10–12, and 14–16 weeks of age. There were no safety concerns and no evidence of any effect of co-administration with rotavirus vaccine.
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U2 - 10.1016/j.jvacx.2022.100216
DO - 10.1016/j.jvacx.2022.100216
M3 - Article
AN - SCOPUS:85138209439
SN - 2590-1362
VL - 12
JO - Vaccine: X
JF - Vaccine: X
M1 - 100216
ER -
